This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this project is to determine the role of viral pathogens in the development of vascular diseases such as atherosclerosis, restenosis, and transplant vascular sclerosis (TVS). All of these diseases are the result of either mechanical or immune-mediated injury followed by inflammation and subsequent smooth muscle cell (SMC) proliferation and migration from the vessel media to the intima, which culminates in vessel narrowing. Clinical studies have directly associated human cytomegalovirus (HCMV) with the acceleration of TVS and vascular restenosis following angioplasty as well as atherosclerosis. Chemokine receptors are known to play an important role in the development of vasculopathies and we hypothesize that the CMV chemokine receptors are integral in the acceleration of this disease process. Recently, we have developed a mouse heart transplantation model of TVS that exhibits all the hallmarks of the human disease. The MCMV heart transplant model offers a unique system to quantitatively assess the mechanisms of virus-accelerated vasculopathy using both viral and mouse genetics. This project will use the in vitro and in vivo systems to elucidate the role of CMV chemokine receptors in virus accelerated vasculopathy.